| Titre |
Phase I Trial of ZW25 in Patients With Locally Advanced (Unresectable) and/or Metastatic HER2-expressing Cancers |
| Protocole ID |
ZWI-ZW25-101 |
| ClinicalTrials.gov ID |
NCT02892123 |
| Type(s) de cancer |
Sein |
| Phase |
Phase I |
| Stade |
Maladie avancée ou métastatique |
| Type étude |
Traitement |
| Médicament |
ZW25 |
| Institution |
CIUSSS DU CENTRE-OUEST-DE-L'ILE-DE-MONTREAL
 HOPITAL GENERAL JUIF SIR MORTIMER B.DAVIS
3755 rue de la Côte Ste. Catherine, Montréal, QC, H3T 1E2
|
| Ville |
Montréal |
| Investigateur(trice) principal(e) |
Dr Cristiano Ferrario
|
| Coordonnateur(trice) |
Ewa Forczek
514-340-8222 poste 26754
|
| Statut |
![]() Fermé |
| Critètes d'éligibilité |
-
HER2-expressing cancer as follows:
Part 1:
Any locally advanced (unresectable) and/or metastatic HER2-expressing (HER2 1+, 2+, or 3+ by IHC) cancer that has progressed after receipt of all therapies known to confer clinical benefit
Part 2:
− Locally advanced (unresectable) and/or metastatic cancer that has progressed after receipt of all therapies know to confer clinical benefit (unless ineligible to receive a specific therapy) as follows:
Part 3:
Locally advanced (unresectable) and/or metastatic cancer as follows:
- HER2-overexpressing (3+ by IHC) or HER2 2+ and FISH positive breast cancer must have progressed after prior treatment with trastuzumab, pertuzumab, and T?DM1
- HER2-overexpressing (3+ by IHC) or HER2 2+ and FISH positive gastric cancer must have progressed after prior treatment with trastuzumab
- Cohort 1: HER2 IHC 2+/FISH negative breast cancer
- Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH positive breast cancer
- Cohort 3: HER2 IHC 2+/FISH negative gastric/GEJ cancer
- Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH positive gastric/GEJ cancer
-
Cohort 5: Any other HER2 IHC 3+ or FISH positive cancer
- Pts with colorectal cancer must be KRAS wild-type
- Pts with NSCLC must have ALK wild-type, EGFR wild-type, and ROS1 fusion negative
- HER2 IHC 1+ or IHC2+/FISH- breast cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens
- HER2 IHC 3+ or IHC 2+/FISH+ breast cancer patients who have received prior therapy with trastuzumab, pertuzumab, and T-DM1, at least 1 and no more than 3 prior systemic chemotherapy regimens
- HER2 IHC 2+ or 3+ FISH+ or FISH- gastric/GEJ cancer patients who have received at least 1 and no more than 3 prior systemic chemotherapy regimens.
- ≥ 18 years of age
- ECOG 0 or 1
-
Adequate hepatic function, as follows:
- AST ≤2.5 x ULN (if liver or bone mets are present, ≤5 x ULN)
- ALT ≤2.5 x ULN (if liver or bone metastases are present, ≤5 x ULN)
- Total bilirubin ≤1.5 x ULN
- Adequate renal function (within normal limits or calculated glomerular filtration rate >50)
-
Hematological function:
- ANC ≥1.5 x 10?/L
- Platelet count ≥75 x 10?/L (Parts 1 and 2), ≥100 x 10?/L (Part 3)
- Hemoglobin ≥9 g/dL
- PT and PTT <1.5 x ULN
- Adequate cardiac left ventricular function
- For Part 1, cohorts 1-3: evaluable disease (per RECIST version 1.1). For Part 1, cohorts 4-6 and Parts 2 and 3: measurable disease (per RECIST version 1.1)
-
Able to provide a fresh formalin-fixed, paraffin-embedded (FFPE) tumor sample for central evaluation of HER2 status prior to enrolment; if a fresh biopsy is not feasible, sponsor approval is required and archived tumor biopsy must be provided for centralized testing by sponsor
- For Parts 1 and 3, eligibility may be based on local read of fresh or archived tumor biopsy. Archived or fresh FFPE biopsy must be provided for retrospective centralized review.
- Willingness to use 2 methods of birth control during the study and for 12 months after the last dose of ZW25
|
| Critètes d'exclusion |
- Experimental therapies within 4 weeks before first ZW25 dosing
- Other cancer therapy including chemotherapy, small molecules, and antibodies within 5 half-lives of the cancer therapy before first ZW25 dosing
- Anthracyclines within 90 days before first ZW25 dosing or lifetime load exceeding 300 mg/m² adriamycin or equivalent
- Trastuzumab, pertuzumab, lapatinib, or T?DM1 within 3 weeks before first ZW25 dosing
- Untreated brain metastases (pts with treated brain mets who are off steroids and anticonvulsants and stable for at least 1 month at the time of Screening are eligible)
- Pregnant or breast-feeding women
- History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in drug formulation
- Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment)
- Peripheral neuropathy >Grade 2
- Clinically significant interstitial lung disease
- Known active hepatitis B or C or known infection with HIV
- Immunosuppressive corticosteroids equivalent to >15mg/day of prednisone within 2 weeks before first ZW25 dose
- QTc Fridericia (QTcF) >450 ms
- Having clinically significant cardiac disease such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic CHF
- Having known myocardial infarction or unstable angina within 6 months before first ZW25 dosing
|
Groupe d'étude en oncologie du Québec